Despite numerous advances in high throughput screening (HTS) and system automation, the identification of specific ligands remains time consuming and resource intensive. A major obstacle to more efficient screening of potential ligands is the current requirement for each target protein to be screened individually. A highly effective method for identifying proteins bound to solid supports is matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). But variability in protein-matrix interactions can make accurate assessments of protein binding difficult, since the absence of mass signal could signify either the absence of binding or the poor desorption/ionization behavior of a particular protein/matrix pair. This ambiguity can be resolved, however, by employing a second, independent measure of binding that is not subject to the same protein-to-protein variability. To this end, we propose the development of a novel discovery platform for the combinatorial analysis of molecular arrays, incorporating metal enhanced fluorescence (MEF) to detect protein binding, and MALDI mass spectrometry to identify the proteins involved.